Central to immune responses is the activation, clonal expansion and differentiation of lymphocytes that carry receptors specific for the immunizing antigen. Upon antigen binding by receptor immunoglobulin (mIgM and mIgD) on B lymphocytes, signals are generated and transduced across the cell membrane which lead to rapid plasma membrane depolarization coupled to a subsequent increase in expression of membrane Ia antigens. Recent evidence suggests that sequential increased phosphatidylinositol (PI) hydrolysis and protein kinase C activation may be coupling events between receptor occupancy and membrane depolarization. We propose here to further examine the role of these events in mIg mediated signal transduction and to define possible mechanisms by which receptor crosslinking may lead to increased phospholipid turnover. In view of evidence that receptor mIgM and mIgD expressed on the same cell may function differently, we will also define and compare effects of independent crosslinking of these receptors on phospholipid metabolism and protein phosphorylation. Specifically, we propose to define and compare the effects of fragments of control antibodies and antibodies specific for mouse Fab, IgM and IgD on B cell phospholipid metabolism and protein phosphorylation. We will determine the effects of receptor immunoglobulin crosslinking on cellular phospholipase C activity and localization, and on phospholipid compartmentalization within the cell membrane. If phospholipid recompartmentalization is observed, we will determine, using a reconstituted liposome system, if this phenomenon is responsible for increased phosphotidylinositol hydrolysis by phospholipase C. Results will contribute significantly to our understanding of the mechanism of mIg mediated transmembrane signaling.